Characterization and Fluctuations of an Ivermectin Binding Site at the Lipid Raft Interface of the N-Terminal Domain (NTD) of the Spike Protein of SARS-CoV-2 Variants.

ABSTRACT: Most studies on the docking of ivermectin on the spike protein of SARS-CoV-2 concern the receptor binding domain (RBD) and, more precisely, the RBD interface recognized by the ACE2 receptor. The N-terminal domain (NTD), which controls the initial attachment of the virus to lipid raft gangliosides, has not received the attention it deserves. In this study, we combined molecular modeling and physicochemical approaches to analyze the mode of interaction of ivermectin with the interface of the NTD-facing lipid rafts of the host cell membrane. We characterize a binding area that presents point mutations and deletions in successive SARS-CoV-2 variants from the initial strain to omicron KP.3 circulating in many countries in 2024. We show that ivermectin has exceptional flexibility, allowing the d

SUBMITTER: Lefebvre M 

PROVIDER: S-EPMC11680242 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature